Acacetin‐induced cell apoptosis in head and neck squamous cell carcinoma cells: Evidence for the role of muscarinic M3 receptor
Aacacetin, a plant flavone has shown antitumor efficacy recently. However, its associated mechanisms are poorly known. We hypothesized that the muscarinic M3 receptor (M3R), which is highly expressed in some cancer tissue, is related to the antitumor effect of acacetin in head and neck squamous cell...
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| Veröffentlicht in: | Phytotherapy research 2019-05, Vol.33 (5), p.1551-1561 |
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| creator | Sun, Fenglin Li, Duo Wang, Cong Peng, Caixia Zheng, Hong Wang, Xiaofeng |
| description | Aacacetin, a plant flavone has shown antitumor efficacy recently. However, its associated mechanisms are poorly known. We hypothesized that the muscarinic M3 receptor (M3R), which is highly expressed in some cancer tissue, is related to the antitumor effect of acacetin in head and neck squamous cell carcinoma (HNSCC) cells. Our results showed that 12.5‐ to 200‐μM acacetin inhibited cell viability in dose‐ and time‐dependent manners in HNSCC cells, but a relative higher concentration was needed for oral adenoid cystic carcinoma cells. M3R expression level was higher in HNSCC cells than that in adenoid cystic carcinoma cells. Flow cytometry and electron microscopy confirmed acacetin‐induced cell apoptosis in 22B cells, a HNSCC cell line. Acacetin promoted mitochondrial cytochrome c release and caspase 9, 3 processing. Knocking down of M3R expression by specific siRNA significantly prevented the acacetin‐induced cell viability damage, cell apoptosis, and caspase 3 activation. Besides, M3R was also involved in acacetin‐induced elevation of reactive oxygen species and intracellular calcium ([Ca2+]i). These data indicate that acacetin‐induced cell apoptosis in HNSCC cells may through M3R related calcium signaling and caspase 3 activation. Acacetin is a potent natural antitumor reagent especially for the tumor cells, which highly expressed M3R. |
| doi_str_mv | 10.1002/ptr.6343 |
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However, its associated mechanisms are poorly known. We hypothesized that the muscarinic M3 receptor (M3R), which is highly expressed in some cancer tissue, is related to the antitumor effect of acacetin in head and neck squamous cell carcinoma (HNSCC) cells. Our results showed that 12.5‐ to 200‐μM acacetin inhibited cell viability in dose‐ and time‐dependent manners in HNSCC cells, but a relative higher concentration was needed for oral adenoid cystic carcinoma cells. M3R expression level was higher in HNSCC cells than that in adenoid cystic carcinoma cells. Flow cytometry and electron microscopy confirmed acacetin‐induced cell apoptosis in 22B cells, a HNSCC cell line. Acacetin promoted mitochondrial cytochrome c release and caspase 9, 3 processing. Knocking down of M3R expression by specific siRNA significantly prevented the acacetin‐induced cell viability damage, cell apoptosis, and caspase 3 activation. Besides, M3R was also involved in acacetin‐induced elevation of reactive oxygen species and intracellular calcium ([Ca2+]i). These data indicate that acacetin‐induced cell apoptosis in HNSCC cells may through M3R related calcium signaling and caspase 3 activation. Acacetin is a potent natural antitumor reagent especially for the tumor cells, which highly expressed M3R.</description><identifier>ISSN: 0951-418X</identifier><identifier>EISSN: 1099-1573</identifier><identifier>DOI: 10.1002/ptr.6343</identifier><identifier>PMID: 31066474</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>acacetin ; Acetylcholine receptors (muscarinic) ; Activation ; Adenoid ; Anticancer properties ; Antitumor activity ; Apoptosis ; Calcium ; Calcium (intracellular) ; Calcium ions ; Calcium signalling ; Cancer ; Caspase ; Caspase-3 ; Caspase-9 ; cell apoptosis ; Cell viability ; Cytochrome ; Cytochrome c ; Cytochromes ; Electron microscopy ; Flow cytometry ; Head & neck cancer ; head and neck squamous cell carcinoma ; Mitochondria ; muscarinic M3 receptor ; Reactive oxygen species ; Reagents ; siRNA ; Squamous cell carcinoma ; Time dependence ; Tumor cells</subject><ispartof>Phytotherapy research, 2019-05, Vol.33 (5), p.1551-1561</ispartof><rights>2019 John Wiley & Sons, Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3493-dd2a384f6631454641569eb78b74f1dcfb7de043a77253be86f26e6939dba0093</citedby><cites>FETCH-LOGICAL-c3493-dd2a384f6631454641569eb78b74f1dcfb7de043a77253be86f26e6939dba0093</cites><orcidid>0000-0002-3020-3322</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fptr.6343$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fptr.6343$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,777,781,1412,27905,27906,45555,45556</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31066474$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sun, Fenglin</creatorcontrib><creatorcontrib>Li, Duo</creatorcontrib><creatorcontrib>Wang, Cong</creatorcontrib><creatorcontrib>Peng, Caixia</creatorcontrib><creatorcontrib>Zheng, Hong</creatorcontrib><creatorcontrib>Wang, Xiaofeng</creatorcontrib><title>Acacetin‐induced cell apoptosis in head and neck squamous cell carcinoma cells: Evidence for the role of muscarinic M3 receptor</title><title>Phytotherapy research</title><addtitle>Phytother Res</addtitle><description>Aacacetin, a plant flavone has shown antitumor efficacy recently. However, its associated mechanisms are poorly known. We hypothesized that the muscarinic M3 receptor (M3R), which is highly expressed in some cancer tissue, is related to the antitumor effect of acacetin in head and neck squamous cell carcinoma (HNSCC) cells. Our results showed that 12.5‐ to 200‐μM acacetin inhibited cell viability in dose‐ and time‐dependent manners in HNSCC cells, but a relative higher concentration was needed for oral adenoid cystic carcinoma cells. M3R expression level was higher in HNSCC cells than that in adenoid cystic carcinoma cells. Flow cytometry and electron microscopy confirmed acacetin‐induced cell apoptosis in 22B cells, a HNSCC cell line. Acacetin promoted mitochondrial cytochrome c release and caspase 9, 3 processing. Knocking down of M3R expression by specific siRNA significantly prevented the acacetin‐induced cell viability damage, cell apoptosis, and caspase 3 activation. Besides, M3R was also involved in acacetin‐induced elevation of reactive oxygen species and intracellular calcium ([Ca2+]i). These data indicate that acacetin‐induced cell apoptosis in HNSCC cells may through M3R related calcium signaling and caspase 3 activation. Acacetin is a potent natural antitumor reagent especially for the tumor cells, which highly expressed M3R.</description><subject>acacetin</subject><subject>Acetylcholine receptors (muscarinic)</subject><subject>Activation</subject><subject>Adenoid</subject><subject>Anticancer properties</subject><subject>Antitumor activity</subject><subject>Apoptosis</subject><subject>Calcium</subject><subject>Calcium (intracellular)</subject><subject>Calcium ions</subject><subject>Calcium signalling</subject><subject>Cancer</subject><subject>Caspase</subject><subject>Caspase-3</subject><subject>Caspase-9</subject><subject>cell apoptosis</subject><subject>Cell viability</subject><subject>Cytochrome</subject><subject>Cytochrome c</subject><subject>Cytochromes</subject><subject>Electron microscopy</subject><subject>Flow cytometry</subject><subject>Head & neck cancer</subject><subject>head and neck squamous cell carcinoma</subject><subject>Mitochondria</subject><subject>muscarinic M3 receptor</subject><subject>Reactive oxygen species</subject><subject>Reagents</subject><subject>siRNA</subject><subject>Squamous cell carcinoma</subject><subject>Time dependence</subject><subject>Tumor cells</subject><issn>0951-418X</issn><issn>1099-1573</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNp1kctq3DAUhkVIaabTQp4gCLLJxqluluzuwpBeIKWlTKE7I0vHRKktOZKdkl3yBn3GPkk1M0kIha4OBz6-8x9-hA4pOaWEsLfjFE8lF3wPLSip64KWiu-jBalLWgha_ThAr1K6IoTUjIiX6IBTIqVQYoHuz4w2MDn_5-6383Y2YLGBvsd6DOMUkkvYeXwJ2mLtLfZgfuJ0PeshzGkHGh2N82HQ2zW9w-c3zoI3gLsQ8XQJOIYecOjwMKcMO-8M_sxxBAP5QnyNXnS6T_DmYS7R9_fn69XH4uLLh0-rs4vCcFHzwlqmeSU6KTkVpZCClrKGVlWtEh21pmuVBSK4VoqVvIVKdkyCrHltW50f50t0svOOMVzPkKZmcGkTWXvIzzSMcVqVJWcyo8f_oFdhjj6n21JcEaaeCU0MKUXomjG6QcfbhpJmU0uTa2k2tWT06EE4twPYJ_CxhwwUO-CX6-H2v6Lm6_rbVvgXQS6XWQ</recordid><startdate>201905</startdate><enddate>201905</enddate><creator>Sun, Fenglin</creator><creator>Li, Duo</creator><creator>Wang, Cong</creator><creator>Peng, Caixia</creator><creator>Zheng, Hong</creator><creator>Wang, Xiaofeng</creator><general>Wiley Subscription Services, Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-3020-3322</orcidid></search><sort><creationdate>201905</creationdate><title>Acacetin‐induced cell apoptosis in head and neck squamous cell carcinoma cells: Evidence for the role of muscarinic M3 receptor</title><author>Sun, Fenglin ; Li, Duo ; Wang, Cong ; Peng, Caixia ; Zheng, Hong ; Wang, Xiaofeng</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3493-dd2a384f6631454641569eb78b74f1dcfb7de043a77253be86f26e6939dba0093</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>acacetin</topic><topic>Acetylcholine receptors (muscarinic)</topic><topic>Activation</topic><topic>Adenoid</topic><topic>Anticancer properties</topic><topic>Antitumor activity</topic><topic>Apoptosis</topic><topic>Calcium</topic><topic>Calcium (intracellular)</topic><topic>Calcium ions</topic><topic>Calcium signalling</topic><topic>Cancer</topic><topic>Caspase</topic><topic>Caspase-3</topic><topic>Caspase-9</topic><topic>cell apoptosis</topic><topic>Cell viability</topic><topic>Cytochrome</topic><topic>Cytochrome c</topic><topic>Cytochromes</topic><topic>Electron microscopy</topic><topic>Flow cytometry</topic><topic>Head & neck cancer</topic><topic>head and neck squamous cell carcinoma</topic><topic>Mitochondria</topic><topic>muscarinic M3 receptor</topic><topic>Reactive oxygen species</topic><topic>Reagents</topic><topic>siRNA</topic><topic>Squamous cell carcinoma</topic><topic>Time dependence</topic><topic>Tumor cells</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sun, Fenglin</creatorcontrib><creatorcontrib>Li, Duo</creatorcontrib><creatorcontrib>Wang, Cong</creatorcontrib><creatorcontrib>Peng, Caixia</creatorcontrib><creatorcontrib>Zheng, Hong</creatorcontrib><creatorcontrib>Wang, Xiaofeng</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Phytotherapy research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sun, Fenglin</au><au>Li, Duo</au><au>Wang, Cong</au><au>Peng, Caixia</au><au>Zheng, Hong</au><au>Wang, Xiaofeng</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Acacetin‐induced cell apoptosis in head and neck squamous cell carcinoma cells: Evidence for the role of muscarinic M3 receptor</atitle><jtitle>Phytotherapy research</jtitle><addtitle>Phytother Res</addtitle><date>2019-05</date><risdate>2019</risdate><volume>33</volume><issue>5</issue><spage>1551</spage><epage>1561</epage><pages>1551-1561</pages><issn>0951-418X</issn><eissn>1099-1573</eissn><abstract>Aacacetin, a plant flavone has shown antitumor efficacy recently. However, its associated mechanisms are poorly known. We hypothesized that the muscarinic M3 receptor (M3R), which is highly expressed in some cancer tissue, is related to the antitumor effect of acacetin in head and neck squamous cell carcinoma (HNSCC) cells. Our results showed that 12.5‐ to 200‐μM acacetin inhibited cell viability in dose‐ and time‐dependent manners in HNSCC cells, but a relative higher concentration was needed for oral adenoid cystic carcinoma cells. M3R expression level was higher in HNSCC cells than that in adenoid cystic carcinoma cells. Flow cytometry and electron microscopy confirmed acacetin‐induced cell apoptosis in 22B cells, a HNSCC cell line. Acacetin promoted mitochondrial cytochrome c release and caspase 9, 3 processing. Knocking down of M3R expression by specific siRNA significantly prevented the acacetin‐induced cell viability damage, cell apoptosis, and caspase 3 activation. Besides, M3R was also involved in acacetin‐induced elevation of reactive oxygen species and intracellular calcium ([Ca2+]i). These data indicate that acacetin‐induced cell apoptosis in HNSCC cells may through M3R related calcium signaling and caspase 3 activation. Acacetin is a potent natural antitumor reagent especially for the tumor cells, which highly expressed M3R.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>31066474</pmid><doi>10.1002/ptr.6343</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-3020-3322</orcidid></addata></record> |
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| subjects | acacetin Acetylcholine receptors (muscarinic) Activation Adenoid Anticancer properties Antitumor activity Apoptosis Calcium Calcium (intracellular) Calcium ions Calcium signalling Cancer Caspase Caspase-3 Caspase-9 cell apoptosis Cell viability Cytochrome Cytochrome c Cytochromes Electron microscopy Flow cytometry Head & neck cancer head and neck squamous cell carcinoma Mitochondria muscarinic M3 receptor Reactive oxygen species Reagents siRNA Squamous cell carcinoma Time dependence Tumor cells |
| title | Acacetin‐induced cell apoptosis in head and neck squamous cell carcinoma cells: Evidence for the role of muscarinic M3 receptor |
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